Urethane and NNK are known to induce a variety of cancers. Urethane has induced lung cancer and liver cancer in mouse in a dose dependent manner, and the safety dose (virtually safe dose, VSD) thereof in human have been calculated to be 1.8×10.−4 mg/kg bodyweight for lung cancer, and 7.2×105 mg/kg body weight for liver cancer, respectively (K. Inai et. al., Jpn. J. Cancer Res.,82, pp. 380-385, April, 1991).
Progeny of the mouse treated by urethane during pregnancy and lactation period have developed significantly increased embryotic cancer, lung cancer and ovarian cystadenoma through placenta, and parent pregnant mouse also have developed endometrial hyperplasia and uterus hemangioma (T. Nomura, Cancer Research, 33, 1677-1683, July, 1973).
Orally administered urethane has induced lung cancer, lymphoma, liver cancer, gastric papilloma, sebaceous gland tumor, breast cancer, lung ademoma, tumor of squamous epithelium cell, leukemia, mesenchymoma, and the like (IARC MONOGRAPHS ON THE EVALUATION OF THE CARCINOGENIC RISK OF CHEMICALS TO MAN, vol. 7, pp. 111-131, the views of two IARC Working Groups on the Evaluation of the Carcinogenic Risks of Chemicals to Man which met in Lyon, Feb. 4, to 11, 1974; and Jun. 18 to 24, 1974).
Further, urethane is an object of regulation in Canada, because it is produced in alcohol fermentation and contained at a predetermined level in a brewed beverage such as wine (Ethyl Carbamate in Alcoholic Beverages and Fermented Foods, ACS Symposium Series No. 484, Food Safety Assessment, edited by John W. Finley et al., pp. 419-428, American Chemical Society, 1992; Identification of Volatile Constituents from Grapes, J. Agric. Food Chem., vol. 24, no. 2, pp. 329-331, 1976; RATIONALE FOR THE ESTABLISHMENT OF GUIDELINES TO LIMIT ETHYL CARBAMATE LEVELS IN ALCOHOLIC BEVERAGES, BUREAU OF CHEMICAL SAFETY FOOD DIRECTORATE HEALTH PROTECTION BRANCH, HEALTH & WELFARE CANADA, pp. 1-8; Ethylcarbamate in Fermented Beverages and Foods, Cornelius S. Ough, J. Agric. Food Chem., vol. 24, No. 2, pp. 323-327.
NNK is one of the possible carcinogenic substances contained in a tobacco smoke (Djordijevic, M. V. et al., A Comparison of selected components in the mainstream smoke of the leading U.S. and Japanese cigarettes. In: Proceedings of the CORESTA smoke and Technology Meeting, pp. 200-217, Nov. 3 to 8, 1996). The morbidity of lung cancer is increasing significantly in both males and females.
The incidence of lung cancer is highly associated with smoking and alcohol ingestion. The International agency for Research on Cancer suggests that the amount of smoking and the amount of alcohol ingestion tend to increase synergistically in human, and that NNK and urethane ingested thereby are causes of lung cancer incidence.
Lung cancer accounts for 45% and 21.5% of cancer related deaths in males and females, respectively. Currently, lung cancer is becoming a leading cause of death in comparison to heart disease among those who smoke in America.
Accordingly, food ingredients, which prevent the induction of cancer caused by smoking and alcohol ingestion, have been sought.
The mushroom, which is generally called agaricus , belongs to the family Agaricaceae of the division Basidiomycota, and is referred to by the botanical name “Agaricus blazei Murill” and the Japanese name “kawariharatake”. Agaricus (hereinafter, generally referred to as kawariharatake, ABM, or agaricus) has been traditionally used as a medicament in the Piedade region in Sao Paulo, Brazil. It is said that agaricus has a variety of immune activation activities, cancer prevention effects, tumor growth suppression effects, and the like. Currently, it is provided for internal use as health food.
Polysaccharides contained in agaricus include β-1, 6-glucopyranosyl residues and have antitumor activity against Sarcoma 180 (Ebina T et al. (1986), Jpn. J. Cancer Res 77:1034-1042). Extracts from agaricus include (1→4)-α-D-glucan having (1→6)-β branched chain, and have natural killer cell activation activity and selective antitumor activity mediated through apoptosis (Fujimiya Y et al. (1998), Cancer Immunol Immunother 46:147-159). Peptideglycans from agaricus have a direct cytotoxic activity against Meth A tumor cells in a double implanted tumor system and an indirect immune enhancement activity in tumor-bearing mice (Ebina T et al. (1998), Biotherapy 11:259-265). Polysaccharides contained in agaricus change the percentage of spleen Thy1,2-, L3T4 positive cells in a T cell subset of mice (Mizuno Metal. (1998), Biosci. Biotechnol. Biochem. 62:434-437).
These reports suggest that polysaccharides contained in agaricus have cytotoxic activity against tumor cells through an immunomodulation activity.
Thus, there have been many reports that say agaricus extracts have an immune enhancement activity and antitumor activity. However, in order to test the effects of agaricus extract, previous researchers have used in vitro tests or in vivo tests with animals which already have cancer. Accordingly, the effects of agaricus extracts on processes of induction and metastasis of cancer such as lung cancer, large intestine cancer, which are caused by a habit of living such as smoking or alcohol ingestion, have not been studied. It has not been reported that there is a food ingredient having effects on processes of inducing cancer and metastasizing cancer, to the best of inventor's knowledge. It is considered that this is because there is no reliable assay system for evaluating processes of inducing cancer and metastasis of cancer.